Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 11 to 20 of 256

Publication Record

Connections

Myeloid translocation genes differentially regulate colorectal cancer programs.
Parang B, Bradley AM, Mittal MK, Short SP, Thompson JJ, Barrett CW, Naik RD, Bilotta AJ, Washington MK, Revetta FL, Smith JJ, Chen X, Wilson KT, Hiebert SW, Williams CS
(2016) Oncogene 35: 6341-6349
MeSH Terms: Animals, Colorectal Neoplasms, Female, Humans, Male, Mice, Mice, Inbred C57BL, Nuclear Proteins, Repressor Proteins, Signal Transduction, Transcription Factors, Translocation, Genetic, Tumor Suppressor Proteins
Show Abstract · Added June 23, 2016
Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1 mice have progressive depletion of all intestinal secretory cells, and Mtg16 mice have a decrease in goblet cells. Furthermore, both Mtgr1 and Mtg16 mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc-dependent intestinal tumorigenesis. Mtgr1 mice, but not Mtg16 mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of chromatin immunoprecipitation sequencing data sets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1 tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context-dependent effect on intestinal tumorigenesis.
0 Communities
3 Members
0 Resources
13 MeSH Terms
Epithelial PIK3R1 (p85) and TP53 Regulate Survivin Expression during Adaptation to Ileocecal Resection.
Cohran V, Managlia E, Bradford EM, Goretsky T, Li T, Katzman RB, Cheresh P, Brown JB, Hawkins J, Liu SXL, De Plaen IG, Weitkamp JH, Helmrath M, Zhang Z, Barrett TA
(2016) Am J Pathol 186: 1837-1846
MeSH Terms: Adaptation, Physiological, Animals, Blotting, Western, Class Ia Phosphatidylinositol 3-Kinase, Digestive System Surgical Procedures, Disease Models, Animal, Enterocolitis, Necrotizing, Extracellular Matrix Proteins, Gene Expression Regulation, Humans, Immunohistochemistry, Infant, Infant, Newborn, Inhibitor of Apoptosis Proteins, Mice, Mice, Inbred C57BL, Phosphatidylinositol 3-Kinases, Real-Time Polymerase Chain Reaction, Repressor Proteins, Short Bowel Syndrome, Survivin, Tumor Suppressor Protein p53
Show Abstract · Added April 16, 2021
Intestinal adaptation to small-bowel resection (SBR) after necrotizing enterocolitis expands absorptive surface areas and promotes enteral autonomy. Survivin increases proliferation and blunts apoptosis. The current study examines survivin in intestinal epithelial cells after ileocecal resection. Wild-type and epithelial Pik3r1 (p85α)-deficient mice underwent sham surgery or 30% resection. RNA and protein were isolated from small bowel to determine levels of β-catenin target gene expression, activated caspase-3, survivin, p85α, and Trp53. Healthy and post-resection human infant small-bowel sections were analyzed for survivin, Ki-67, and TP53 by immunohistochemistry. Five days after ileocecal resection, epithelial levels of survivin increased relative to sham-operated on mice, which correlated with reduced cleaved caspase-3, p85α, and Trp53. At baseline, p85α-deficient intestinal epithelial cells had less Trp53 and more survivin, and relative responses to resection were blunted compared with wild-type. In infant small bowel, survivin in transit amplifying cells increased 71% after SBR. Resection increased proliferation and decreased numbers of TP53-positive epithelial cells. Data suggest that ileocecal resection reduces p85α, which lowers TP53 activation and releases survivin promoter repression. The subsequent increase in survivin among transit amplifying cells promotes epithelial cell proliferation and lengthens crypts. These findings suggest that SBR reduces p85α and TP53, which increases survivin and intestinal epithelial cell expansion during therapeutic adaptation in patients with short bowel syndrome.
Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Characterization of human papillomavirus antibodies in individuals with head and neck cancer.
Lang Kuhs KA, Pawlita M, Gibson SP, Schmitt NC, Trivedi S, Argiris A, Kreimer AR, Ferris RL, Waterboer T
(2016) Cancer Epidemiol 42: 46-52
MeSH Terms: Head and Neck Neoplasms, Human papillomavirus 16, Humans, Oncogene Proteins, Viral, Papillomavirus Infections, Repressor Proteins, Seroepidemiologic Studies
Show Abstract · Added August 15, 2017
BACKGROUND - Human papillomavirus type 16 (HPV16) E6 antibodies are a promising biomarker of oropharyngeal cancer (OPC); however, seropositivity among non-OPC cases is not well characterized.
METHODS - Pre-treatment sera from 260 (38 OPC, 222 non-OPC) incident head and neck cancers diagnosed at the University of Pittsburgh between 2003 and 2006 were tested for HPV16 (L1,E1,E2,E4,E6,E7) and non-HPV16 E6 (HPV6,11,18,33) antibodies. Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven tumors was evaluated among tumors with known HPV status (n=25).
RESULTS - 63.2% of OPC versus 27.5% of non-OPC cases were HPV16 seropositive; HPV16 E6 seroprevalence was 60.5% and 6.3% respectively, odds ratio 22.8 (95% confidence interval [CI] 9.8-53.1). Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven OPC was 100% [95% CI: 50-100%; n=6] and 100% [95% CI: 60-100%, n=4] compared to 0% (n=2) and 0% (n=13) for non-OPC cases.
CONCLUSIONS - HPV16 antibodies were significantly more common in OPC versus non-OPC cases, particularly HPV16 E6 antibodies.
Copyright © 2016 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
7 MeSH Terms
Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action.
Hempel JE, Cadar AG, Hong CC
(2016) Bioorg Med Chem Lett 26: 1947-53
MeSH Terms: Cyclic Nucleotide Phosphodiesterases, Type 4, Dose-Response Relationship, Drug, HEK293 Cells, Hedgehog Proteins, Humans, Molecular Structure, Phosphodiesterase 4 Inhibitors, Pyrimidinones, Repressor Proteins, Signal Transduction, Smoothened Receptor, Structure-Activity Relationship
Show Abstract · Added March 17, 2016
From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation.
Published by Elsevier Ltd.
1 Communities
1 Members
0 Resources
12 MeSH Terms
Insm1 promotes neurogenic proliferation in delaminated otic progenitors.
Lorenzen SM, Duggan A, Osipovich AB, Magnuson MA, García-Añoveros J
(2015) Mech Dev 138 Pt 3: 233-45
MeSH Terms: Animals, Cell Differentiation, Cell Proliferation, DNA-Binding Proteins, Ear, Inner, Female, Gene Expression Regulation, Developmental, Hair Cells, Auditory, Inner, Hair Cells, Auditory, Outer, Male, Mice, Mice, Knockout, Mice, Transgenic, Neural Stem Cells, Neurogenesis, Pregnancy, RNA, Messenger, Repressor Proteins, Spiral Ganglion, Transcription Factors, Vestibule, Labyrinth, Zinc Fingers
Show Abstract · Added November 14, 2015
INSM1 is a zinc-finger protein expressed throughout the developing nervous system in late neuronal progenitors and nascent neurons. In the embryonic cortex and olfactory epithelium, Insm1 may promote the transition of progenitors from apical, proliferative, and uncommitted to basal, terminally-dividing and neuron producing. In the otocyst, delaminating and delaminated progenitors express Insm1, whereas apically-dividing progenitors do not. This expression pattern is analogous to that in embryonic olfactory epithelium and cortex (basal/subventricular progenitors). Lineage analysis confirms that auditory and vestibular neurons originate from Insm1-expressing cells. In the absence of Insm1, otic ganglia are smaller, with 40% fewer neurons. Accounting for the decrease in neurons, delaminated progenitors undergo fewer mitoses, but there is no change in apoptosis. We conclude that in the embryonic inner ear, Insm1 promotes proliferation of delaminated neuronal progenitors and hence the production of neurons, a similar function to that in other embryonic neural epithelia. Unexpectedly, we also found that differentiating, but not mature, outer hair cells express Insm1, whereas inner hair cells do not. Insm1 is the earliest known gene expressed in outer versus inner hair cells, demonstrating that nascent outer hair cells initiate a unique differentiation program in the embryo, much earlier than previously believed.
Copyright © 2015 Elsevier B.V. All rights reserved.
3 Communities
2 Members
0 Resources
22 MeSH Terms
Inactivating the permanent neonatal diabetes gene Mnx1 switches insulin-producing β-cells to a δ-like fate and reveals a facultative proliferative capacity in aged β-cells.
Pan FC, Brissova M, Powers AC, Pfaff S, Wright CV
(2015) Development 142: 3637-48
MeSH Terms: Animals, Cell Transdifferentiation, Cellular Senescence, Diabetes Mellitus, Eye Proteins, Homeodomain Proteins, Humans, Hyperplasia, Insulin-Secreting Cells, Mice, PAX6 Transcription Factor, Paired Box Transcription Factors, Repressor Proteins, Somatostatin-Secreting Cells, Transcription Factors
Show Abstract · Added December 28, 2015
Homozygous Mnx1 mutation causes permanent neonatal diabetes in humans, but via unknown mechanisms. Our systematic and longitudinal analysis of Mnx1 function during murine pancreas organogenesis and into the adult uncovered novel stage-specific roles for Mnx1 in endocrine lineage allocation and β-cell fate maintenance. Inactivation in the endocrine-progenitor stage shows that Mnx1 promotes β-cell while suppressing δ-cell differentiation programs, and is crucial for postnatal β-cell fate maintenance. Inactivating Mnx1 in embryonic β-cells (Mnx1(Δbeta)) caused β-to-δ-like cell transdifferentiation, which was delayed until postnatal stages. In the latter context, β-cells escaping Mnx1 inactivation unexpectedly upregulated Mnx1 expression and underwent an age-independent persistent proliferation. Escaper β-cells restored, but then eventually surpassed, the normal pancreatic β-cell mass, leading to islet hyperplasia in aged mice. In vitro analysis of islets isolated from Mnx1(Δbeta) mice showed higher insulin secretory activity and greater insulin mRNA content than in wild-type islets. Mnx1(Δbeta) mice also showed a much faster return to euglycemia after β-cell ablation, suggesting that the new β-cells derived from the escaper population are functional. Our findings identify Mnx1 as an important factor in β-cell differentiation and proliferation, with the potential for targeting to increase the number of endogenous β-cells for diabetes therapy.
© 2015. Published by The Company of Biologists Ltd.
0 Communities
3 Members
0 Resources
15 MeSH Terms
Insm1 controls the differentiation of pulmonary neuroendocrine cells by repressing Hes1.
Jia S, Wildner H, Birchmeier C
(2015) Dev Biol 408: 90-8
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cell Transdifferentiation, DNA-Binding Proteins, Homeodomain Proteins, Lung, Mice, Mutant Strains, Mutation, Neuroendocrine Cells, Protein Binding, Repressor Proteins, Transcription Factor HES-1, Transcription Factors
Show Abstract · Added March 29, 2016
Epithelial progenitor cells of the lung generate all cell types of the mature airway epithelium, among them the neuroendocrine cells. The balance between formation of pulmonary neuroendocrine and non-neuroendocrine cells is controlled by Notch signaling. The Notch target gene Hes1 is expressed by non-neuroendocrine and absent in neuroendocrine cells. The transcription factor Ascl1 is expressed in a complementary pattern and provides key regulatory information that specifies the neuroendocrine cell fate. The molecular events that occur after the induction of the neuroendocrine differentiation program have received little attention. Here we show that Insm1 is expressed in pulmonary neuroendocrine cells, and that Insm1 expression is not initiated in the lung of Ascl1 mutant mice. We use mouse genetics to show that pulmonary neuroendocrine cells depend on Insm1 for their differentiation. Mutation of Insm1 blocks terminal differentiation, upregulates Hes1 protein in neuroendocrine cells and interferes with maintenance of Ascl1 expression. We show that Insm1 binds to the Hes1 promoter and represses Hes1, and we propose that the Insm1-dependent Hes1 repression is required for neuroendocrine development. Our work demonstrates that Insm1 is a key factor regulating differentiation of pulmonary neuroendocrine cells.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
1 Communities
0 Members
0 Resources
14 MeSH Terms
Helicobacter pylori adaptation in vivo in response to a high-salt diet.
Loh JT, Gaddy JA, Algood HM, Gaudieri S, Mallal S, Cover TL
(2015) Infect Immun 83: 4871-83
MeSH Terms: Adaptation, Physiological, Animals, Bacterial Proteins, Base Sequence, Disease Models, Animal, Gastric Mucosa, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Genome, Bacterial, Gerbillinae, Helicobacter Infections, Helicobacter pylori, Host-Pathogen Interactions, Humans, Iron, Molecular Sequence Data, Mutation, Oxidative Stress, Proteome, Repressor Proteins, Sodium Chloride, Dietary
Show Abstract · Added October 8, 2015
Helicobacter pylori exhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification of H. pylori is influenced by the composition of the diet. Specifically, we investigated the effect of a high-salt diet (a known risk factor for gastric adenocarcinoma) on H. pylori diversification within a host. We analyzed H. pylori strains isolated from Mongolian gerbils fed either a high-salt diet or a regular diet for 4 months by proteomic and whole-genome sequencing methods. Compared to the input strain and output strains from animals fed a regular diet, the output strains from animals fed a high-salt diet produced higher levels of proteins involved in iron acquisition and oxidative-stress resistance. Several of these changes were attributable to a nonsynonymous mutation in fur (fur-R88H). Further experiments indicated that this mutation conferred increased resistance to high-salt conditions and oxidative stress. We propose a model in which a high-salt diet leads to high levels of gastric inflammation and associated oxidative stress in H. pylori-infected animals and that these conditions, along with the high intraluminal concentrations of sodium chloride, lead to selection of H. pylori strains that are most fit for growth in this environment.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
0 Communities
3 Members
0 Resources
21 MeSH Terms
The MYC-WDR5 Nexus and Cancer.
Thomas LR, Foshage AM, Weissmiller AM, Tansey WP
(2015) Cancer Res 75: 4012-5
MeSH Terms: Antineoplastic Agents, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Chromatin Assembly and Disassembly, DNA, DNA Methylation, Drug Discovery, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Genes, myc, Histone-Lysine N-Methyltransferase, Histones, Humans, Intracellular Signaling Peptides and Proteins, Models, Genetic, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasms, Protein Binding, Proto-Oncogene Proteins c-myc, Repressor Proteins, Signal Transduction
Show Abstract · Added March 26, 2019
The MYC oncogenes encode a family of transcription factors that feature prominently in cancer. MYC proteins are overexpressed or deregulated in a majority of malignancies and drive tumorigenesis by inducing widespread transcriptional reprogramming that promotes cell proliferation, metabolism, and genomic instability. The ability of MYC to regulate transcription depends on its dimerization with MAX, which creates a DNA-binding domain that recognizes specific sequences in the regulatory elements of MYC target genes. Recently, we discovered that recognition of target genes by MYC also depends on its interaction with WDR5, a WD40-repeat protein that exists as part of several chromatin-regulatory complexes. Here, we discuss how interaction of MYC with WDR5 could create an avidity-based chromatin recognition mechanism that allows MYC to select its target genes in response to both genetic and epigenetic determinants. We rationalize how the MYC-WDR5 interaction provides plasticity in target gene selection by MYC and speculate on the biochemical and genomic contexts in which this interaction occurs. Finally, we discuss how properties of the MYC-WDR5 interface make it an attractive point for discovery of small-molecule inhibitors of MYC function in cancer cells.
©2015 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells.
Dutta P, Sager HB, Stengel KR, Naxerova K, Courties G, Saez B, Silberstein L, Heidt T, Sebas M, Sun Y, Wojtkiewicz G, Feruglio PF, King K, Baker JN, van der Laan AM, Borodovsky A, Fitzgerald K, Hulsmans M, Hoyer F, Iwamoto Y, Vinegoni C, Brown D, Di Carli M, Libby P, Hiebert SW, Scadden DT, Swirski FK, Weissleder R, Nahrendorf M
(2015) Cell Stem Cell 16: 477-87
MeSH Terms: Animals, Cell Movement, Cells, Cultured, Hematopoietic Stem Cells, Macrophages, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Models, Animal, Monocytes, Myeloid Cells, Myelopoiesis, Myocardial Infarction, Nuclear Proteins, RNA, Small Interfering, Receptors, CCR2, Repressor Proteins, Transcription Factors, Wound Healing
Show Abstract · Added September 28, 2015
Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. The origin of these myeloid cells, and the response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is unclear. Here, we identify a CCR2(+)CD150(+)CD48(-) LSK hematopoietic subset as the most upstream contributor to emergency myelopoiesis after ischemic organ injury. This subset has 4-fold higher proliferation rates than CCR2(-)CD150(+)CD48(-) LSK cells, displays a myeloid differentiation bias, and dominates the migratory HSPC population. We further demonstrate that the myeloid translocation gene 16 (Mtg16) regulates CCR2(+) HSPC emergence. Mtg16(-/-) mice have decreased levels of systemic monocytes and infarct-associated macrophages and display compromised tissue healing and post-MI heart failure. Together, these data provide insights into regulation of emergency hematopoiesis after ischemic injury and identify potential therapeutic targets to modulate leukocyte output after MI.
Copyright © 2015 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
19 MeSH Terms